Evidence map›Paper›PMID 26041297›Full record

ArticleJournal of virology2015

Inhibition of O-Linked N-Acetylglucosamine Transferase Reduces Replication of Herpes Simplex Virus and Human Cytomegalovirus.

Magdalena Angelova, Rodrigo F Ortiz-Meoz, Suzanne Walker, David M Knipe

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.8field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

20 citing papers in PubMed, 40 citations in OpenAlex.

  1. Article
  2. Article
  3. O-GlcNAc modulation of nuclear pore complexes orchestrates mRNA export efficiency.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Article
  5. Article
  6. Regulations of mFrontiers of medicine · 2024
    Review
  7. Review
  8. O-GlcNAc of STING mediates antiviral innate immunity.Cell communication and signaling : CCS · 2024
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Frontiers in immunology · 2020
    Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Magdalena AngelovaDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Rodrigo F Ortiz-MeozDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
Suzanne WalkerDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA.
David M KnipeDepartment of Microbiology and Immunobiology, Harvard Medical School, Boston, Massachusetts, USA david_knipe@hms.harvard.edu.
Harvard University · US

Funding

Structure, Function and Inhibition of Human O-GlcNAc TransferaseR01GM094263 · NIGMS · HARVARD MEDICAL SCHOOL · PI WALKER, SUZANNE · 2012 to 2024
$5.8M
Genetics of Herpesvirus TransformationR01AI063106 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI KNIPE, DAVID M. · 2004 to 2013
$3.8M
NIAID NIH HHS AI 06310NIAID NIH HHS R01 AI063106NIGMS NIH HHS GM094263NIGMS NIH HHS R01 GM094263
6 · The paper itself

Abstract

unlabelledO-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) is an essential cellular enzyme that posttranslationally modifies nuclear and cytoplasmic proteins via O-linked addition of a single N-acetylglucosamine (GlcNAc) moiety. Among the many targets of OGT is host cell factor 1 (HCF-1), a transcriptional regulator that is required for transactivation of the immediate-early genes of herpes simplex virus (HSV). HCF-1 is synthesized as a large precursor that is proteolytically cleaved by OGT, which may regulate its biological function. In this study, we tested whether inhibition of the enzymatic activity of OGT with a small molecule inhibitor, OSMI-1, affects initiation of HSV immediate-early gene expression and viral replication. We found that inhibiting OGT's enzymatic activity significantly decreased HSV replication. The major effect of the inhibitor occurred late in the viral replication cycle, when it reduced the levels of late proteins and inhibited capsid formation. However, depleting OGT levels with small interfering RNA (siRNA) reduced the expression of HSV immediate-early genes, in addition to reducing viral yields. In this study, we identified OGT as a novel cellular factor involved in HSV replication. Our results obtained using a small molecule inhibitor and siRNA depletion suggest that OGT's glycosylation and scaffolding functions play distinct roles in the replication cycle of HSV. IMPORTANCE: Antiviral agents can target viral or host gene products essential for viral replication. O-GlcNAc transferase (OGT) is an important cellular enzyme that catalyzes the posttranslational addition of GlcNAc sugar residues to hundreds of nuclear and cytoplasmic proteins, and this modification regulates their activity and function. Some of the known OGT targets are cellular proteins that are critical for the expression of herpes simplex virus (HSV) genes, suggesting a role for OGT in the replication cycle of HSV. In this study, we found that OGT is required for efficient expression of viral genes and for assembly of new virions. Thus, we identify OGT as a novel host factor involved in the replication of HSV and a potential target for antiviral therapy.

Indexed as

AnimalsCell LineChlorocebus aethiopsCytomegalovirusElectrophoresis, Polyacrylamide GelEnzyme InhibitorsFluorescent Antibody TechniqueGene Expression Regulation, ViralGenes, Immediate-EarlyHost Cell Factor C1HumansImmunoblottingMicroscopy, ElectronN-AcetylglucosaminyltransferasesReal-Time Polymerase Chain ReactionRNA, Small InterferingEnzyme InhibitorsHCFC1 protein, humanHost Cell Factor C1N-AcetylglucosaminyltransferasesRNA, Small InterferingUDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase

Identifiers

PMID26041297
PMCPMC4524265
OpenAlexW1589191313

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.